Therapy with human recombinant erythropoietin (EPO) has been accepted as effective
for renal anemia in dialysis patients. However, studies in rats have shown that correcting
anemia with EPO may affect the progression of renal dysfunction. In humans, however,
the effect of EPO on residual renal function is a matter of controversy. We, therefore,
investigated whether the long-term administration of EPO to predialysis patients influences
residual renal function. Anemic patients at the predialysis stage with a serum creatinine
(Cr) concentration ranging from 2 to 4 (average 2.9) mg/dl and a hematocrit (Ht) of
less than 30% were randomly assigned to two groups which consisted of anemic patients
not treated with EPO (group I, untreated anemic controls, n = 31) and anemic patients
treated with EPO (group II, treated anemics, n = 42). Patients with nonsevere or moderate
anemia (Ht > 30%) with a Cr ranging from 2 to 4 (average 2.6) mg/dl were also recruited
as nonanemic controls (group III, untreated nonanemic controls, n = 35). Blood pressure
was controlled to the same degree among the three groups by combined treatment with
calcium antagonists and angiotensin-converting enzyme inhibitors. All patients were
kept strictly on a low-protein (0.6 g/kg/day) and a low-salt (7 g/day) diet. The degree
of control of dietary protein and blood pressure and the frequency of angiotensin-converting
enzyme inhibitor administration were comparable among the three groups. The primary
end point for each patient was a doubling of the baseline Cr which yielded cumulative
renal survival rates which were plotted against time. Ht rose significantly from 27.0
± 2.3 to 32.1 ± 3.2% in group II (n = 42, p < 0.001) with a rate of increase of 0.4
± 0.06%/week. However, it declined from 27.9 ± 1.8 to 25.3 ± 1.9% in group I (n =
31, p < 0.001) and from 35.9 ± 3.5 to 32.2 ± 3.9% in group III (n = 35, p < 0.001).
Cr doubled in 26 patients (84%) in group I as compared with 22 (52%) in group II and
21 (60%) in group III. The cumulative renal survival rates in groups II and III were
significantly better than that in group I: p = 0.0003 (group I vs. group II) and p
= 0.0024 (group I vs. group III). However, there was no difference in the renal survival
rate between groups II and III (p = 0.3111). The better survival rate obtained in
group II was attributable to the better survival rate for the nondiabetic patients
in this group. The present study suggests that anemia, per se, is a factor in the
progression of end-stage renal failure and that reversal of anemia by EPO can retard
the progression of renal failure, especially in nondiabetic patiens, provided that
blood pressure control, rate of increase in Ht, and dietary protein restriction are
appropriate.